This is a request for continued support of a National Institute on Drug Abuse Research Scientist Award. The long-term objectives and specific aims of the proposed research focus upon the development of generalizable knowledge relevant to the environmental and behavioral determinants of drug-seeking and drug-taking as these processes bear upon public health concerns related to drug abuse and dependence. More specifically, the proposed investigations will emphasize experimental studies of the reinforcing, discriminative, and physiological dependence- producing functions of drugs of abuse in laboratory animals and human volunteer participants with particular reference to the most commonly abused opioids, sedative"hypnotic"'anxiolytic, and stimulant agents (e.g., heroin, buprenorphine, benzodiazepines, amphetamines, cocaine). Both intravenous and oral routes of administration will be studied and molecular mechanisms of action will be investigated. Investigations will also be undertaken to determine the acute and chronic effects upon sensory and motor functions of such drugs of abuse both singly and in combination so as to develop an appropriate behavioral toxicity data base in laboratory primates. These studies will involve applications and extensions of animal psychophysical methods for assessment of drug effects upon auditory and visual thresholds, reaction times, and vowel discrimination functions. Additional studies will examine the determinants and consequences of drug- seeking and drug-taking in human volunteers with a focus upon the role of family history involving substance abuse (e.g., alcoholism) in modulating physiological, psychomotor, subjective, and behavioral responses to marijuana. And continuation of collaborative projects with the Baltimore City Health Department and local research groups will extend these drug abuse research initiatives to new studies assessing cost effectiveness. The interrelationships between these several aspects of scientific inquiry and the long-term objectives of the proposed research to enhance the knowledge base relevant to drug dependence potential and abuse liability is to be understood within the unifying conceptual framework of an environmental/behavioral model for integrating the multiple interacting levels of investigative effort focused upon drug-seeking and drug-taking as critical aspects of public health concern.